Hail mighty Celator, the small cap that beat long odds

Remember the plucky US microcap Celator Pharmaceuticals, pitching its Vyxeos liposomal reformulation of cytarabine and daunorubicin up against the traditional “7+3" regimen of those two agents in acute myeloid leukaemia? Not content with trialling its lead drug in one of the industry’s most famously difficult indications, it was at the same time testing the notorious Feuerstein-Ratain rule.  

Last night it emerged a victor over both the standard of care in AML and the FR rule – which predicts clinical failure for sub-$300m market cap cancer companies – with a stunning phase III trial result. Surprised investors boosted its share price by over 370% this morning, pushing its valuation up to $300m and well into small-cap territory.  

Celator’s 309-patient phase III trial, named 301, showed a statistically significant 3.61 month improvement in median overall survival for Vyxeos relative to 7+3, equivalent to a 31% reduction in the risk of death. It enrolled patients aged 60 to 75 with secondary AML – those whose disease arose as a result of myelodysplastic syndromes or was caused by prior therapy for another cancer type.

This is considered one of the hardest AML subgroups to treat, and its selection was driven by ethical considerations as it would have been hard to test Vyxeos against 7+3 in younger, de novo AML patients in a randomised trial. Now that the 301 study has established Vyxeos as superior in terms of efficacy, safety and convenience compared with 7+3 in secondary AML, physicians are likely to use it in preference to the conventional regimen for all patients.  

Results from phase III 301 trial of Vyxeos
Measure  Vyxeos 7+3  Statistical analysis
Median OS 9.56 months  5.95 months  HR=0.69, p=0.005  
% of pts alive at 12 months  41.5% 27.6%
% of pts alive at 24 months 31.1% 12.3%
Induction response rate (CR+CRi)   47.7% 33.3% p=0.016
Induction response rate (CR) 37.3% 25.6% p=0.040
60-day all cause mortality 13.7% 21.2%

The 7+3 regimen is so named for its scheduling of seven days of cytarabine, given by continuous IV infusion, with three days of days of an anthracycline, usually daunorubicin, given by IV bolus on days 1-3.

Vyxeos, however, was administered in lower cumulative doses, with a simpler schedule: a 90-minute infusion every other day, yet still got better results. The liposomal formulation improves plasma half-life and permits a lower notional dose per cycle of both cytarabine and daunorubicin, but achieves greater cumulative exposure of the two drugs.

7+3 has been the standard first-line therapy for AML for almost 40 years, but the regimen is highly cytotoxic and comes with serious side effects including severe anaemia and the risk of serious bacterial and fungal infections, which contribute to treatment-related deaths. The treatment has to be administered in hospital so patients can receive supportive care, and the toxicity is such that it is reserved for younger, fitter patients, usually those under age 60.  

Celator’s success means AML – a field that has been bereft of innovation for many years – will likely see two new agents introduced by the end of next year. Novartis recently scored a rare success with its FLT-3 inhibitor midostaurin, which showed a 23% improvement in OS in combination with 7+3 in patients harbouring FLT-3 mutations.

Haematologists now have much to look forward to. The field remains active with several other agents in phase III development, including Boehringer Ingelheim’s volasertib, which is due to render results later this year (Hopes rise for a breakthrough in leukaemia logjam, February 25, 2016).

Celator’s success must surely make it a target for companies looking to establish a bridgehead in AML while at the same time giving it the luxury of being able to raise new equity at a more attractive price.

Celator’s meteoric share price rise, together with that of GW Pharmaceuticals yesterday, also highlights a phenomenon of the current biotech bear market: positive phase III results still retain their value and huge gains can be made if investors predict these correctly. 

To contact the writer of this story email Robin Davison in London at news@epvantage.com or follow @RobinDavison2 on Twitter

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